ADH1C gene was strongly associated with alcohol dependence (P = 1.4 × 10−4) even though it did not meet strict standards for genome-wide multiple testing. Two subsequent studies have identified a SNP in PKNOX2 (rs10893366, P = 1.9 × 10–7) and a cluster of SNPs on chromosome 11 (P < 10−5) that also are associated with alcohol dependence but did not meet the level of statistical significance (Bierut et al. 2010; Edenberg et al. 2010). A fourth GWASs of quantitative indices of excessive alcohol consumption recently was completed in a large cohort of Australian families, in which no genetic variant met the standards for genome-wide significance (Heath et al. 2011). Across the four studies, there was no evidence for replication of any genetic signals, raising the possibility that the identified signals were false positives or that true signals could not be detected as a result of the (by GWASs standards) relatively small sample sizes (i.e., several thousand subjects).
